Conservation of fiber structure and CD46 usage by subgroup B2 adenoviruses.
Conservation of fiber structure and CD46 usage by subgroup B2 adenoviruses.
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DOI：
10.1016/j.virol.2008.02.013
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发表时间：
2008-06
期刊：
影响因子：
3.7
通讯作者：
L. Pache;Sangita Venkataraman;G. Nemerow;V. Reddy
中科院分区：
文献类型：
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作者：
L. Pache;Sangita Venkataraman;G. Nemerow;V. Reddy
大多数B2亚群腺病毒使用CD46作为其主要受体。最近的结构和诱变研究表明，Ad11和Ad35可能以非常相似的方式与该受体结合。然而，目前还没有对不同Ad纤维的细胞相关CD46结合效率进行比较研究。我们求解了Ad35纤维旋钮的晶体结构，并建立了Ad35纤维旋钮与CD46络合的模型。我们的模型与Ad11 - cd46的模型比较表明，尽管Ad11的IJ环中有更大的cd46相互作用区域，但隐藏的表面积非常相似，这表明两种纤维旋钮可能具有相似的结合。为了支持这一点，基于细胞的竞争研究表明，Ad11和Ad35纤维与细胞表面CD46的结合效率几乎相同。这些发现进一步揭示了CD46与Ad的关联，并可能影响基因转移的新型Ad类型的选择。
Most subgroup B2 adenoviruses use CD46 as their primary receptor. Recent structural and mutagenesis studies suggested that Ad11 and Ad35 likely engage this receptor in a very similar fashion. However, no comparative studies assessing the cell-associated CD46 binding efficiencies of different Ad fibers have been performed. We solved the crystal structure of Ad35 fiber knob and constructed a model of the fiber knob complexed with CD46. Comparison of our model with that of Ad11–CD46 showed that despite a larger CD46-interacting region in the IJ loop of Ad11, the buried surface area was very similar, suggesting that both fiber knobs might exhibit similar binding. In support of this, cell based competition studies demonstrated almost identical binding efficiencies of Ad11 and Ad35 fibers to cell surface CD46. These findings shed further light on CD46 association by Ad and could impact the selection of novel Ad types for gene transfer.